Open AccessStructural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors
Author(s) -
Lee Youngjin,
Ryu Young Bae,
Youn HyungSeop,
Cho Jung Keun,
Kim Young Min,
Park JiYoung,
Lee Woo Song,
Park Ki Hun,
Eom Soo Hyun
Publication year - 2014
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s1399004714002971
Subject(s) - sialidase , natural (archaeology) , chemistry , biochemistry , pharmacology , medicine , enzyme , biology , neuraminidase , paleontology
Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp ‐NanI, a sialidase from Clostridium perfringens , are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp ‐NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme–inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti‐sialidase agents.